1. Field of the Invention
The invention generally relates to photodynamic therapy agents. In particular, the invention provides tunable supramolecular metallic complexes which can be activated to cleave DNA by low energy light and in the absence of O2.
2. Background of the Invention
Photodynamic therapy (PDT) is currently gaining acceptance for the treatment of hyperproliferating tissues such as cancers and non-malignant lesions. Significant emphasis has been placed on developing photochemical reagents capable of cleaving DNA for such purposes. Photochemical approaches are of particular interest as they offer reaction control and can be highly targeted.
One popular approach in the design of photodynamic agents involves the sensitization of molecular oxygen. Typically, such agents absorb light energy and transfer that energy to molecular oxygen to generate a reactive singlet oxygen state 1O2. The 1O2 state is highly reactive and, in an intracellular environment, 1O2 randomly reacts with and damages biomolecules and subcellular components, leading to potentially lethal damage to the cell. However, the use of such agents has several drawbacks. For example, the wavelengths of light that must be used to activate this type of photodynamic agent are short wavelength/high energy and cause extensive damage to healthy tissue adjacent to the targeted, hyperproliferating cells. The targeted cell may lyse, releasing 1O2 into the immediate environment where it continues to react randomly with and damage healthy tissue in the area. Further, such agents require the presence of oxygen, the level of which is relatively low in an intracellular environment. Finally, there is an overall lack of flexibility in the design of such agents.
It is thus of interest to develop photosensitizing agents for photodynamic therapy with alternative mechanisms of action. In particular, it would be of benefit to have available photosensitizing agents that absorb and are activated by low energy light. The use of photosensitizing agents that absorb low energy light is less likely to cause unwanted collateral damage to non-targeted cells in a photodynamic therapy setting. In addition, it would be of benefit to have available photosensitizing agents that function efficiently in the absence of molecular oxygen as such agents would be particularly suitable for intracelluar use. Further, it would be highly desirable to have available tunable photosensitizing agents, i.e. photosensitizing agents with a flexible architectural motif that can be readily adjusted or tailored for use in specific applications.